Generation of activated killer cells in tumor-bearing hosts.

Activated killer (AK) cells were generated in spleen-cell cultures derived from tumor-bearing hosts (TS) whereas, under the same conditions, cultured normal spleen cells (NS) gave little cytotoxicity. The AK effectors were primarily Thy1+, AGM1- and Lyt2- and thus were neither classic cytotoxic T lymphocytes (CTL) nor classic NK cells. These AK cells selectively killed tumor targets of different etiologic origins and did not kill concanavalin-A-induced lymphoblasts. The broad target-cell reactivity of these AK cells was also confirmed by cold target-inhibition experiments. Generation of AK cell correlated with interleukin-2 (IL-2) production, and the levels of AK cells generation paralleled those of IL-2 production. Furthermore, the generation of AK cells was blocked by the anti-IL-2 receptor monoclonal antibody (MAb) (alpha IL-2R), indicating that IL-2 was involved, and thus these AK cells were lymphokine-activated killer (LAK) cells. We previously showed that the expression of AGM1 on LAK precursors disappeared when they differentiated into LAK effectors, indicating that the activated LAK cells lacked AGM1. When examining the serologic phenotype of the LAK precursors in tumor-bearing hosts, we found that they lacked AGM1, which suggested that these LAK precursors were in an "activated" state. These cells were still Thy1-, and were thus different from fully activated LAK effectors which were Thy1+ cells, indicating that the full differentiation of LAK cells in vivo was arrested in the tumor-bearing hosts. We also found that the presence of small amounts of X-irradiated tumor cells prevented the generation of AK cells. These findings suggest that, in the tumor-bearing hosts, the presence of tumor cells triggers the activation of AK precursors; however, the same tumor cells may also be immunosuppressive, which prevents the full differentiation of AK precursors into AK effectors.